Research Interests

Clinical Trials

Identification of Potential New Therapies for Myeloproliferative Neoplasms Read more

Associations/Memberships

American Society of Hematology (ASH)

American Association for Cancer Research (AACR)

Publications

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Research Abstract

Hematopoiesis is an important biological process in which small numbers of self-renewing hematopoietic stem cells (HSC) generate large numbers of mature blood cells of multiple distinct lineages. This orderly process is regulated by signal transduction cascades mediated by cytokines and their receptors, and requires appropriate balance of cell proliferation, differentiation, adhesion, migration, survival and death. Abnormal regulation of this process can cause myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) or leukemia. Understanding the signaling pathways that regulate the normal hematopoiesis, and determining how these signaling pathways are deranged in diseases is important for the rational development of new therapies for blood diseases.

Many hematopoietic signaling pathways are controlled by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). JAK2, a member of the Janus family of non-receptor PTKs, is activated in response to a variety of cytokines. A Somatic mutation (V617F) in JAK2 has been found in a majority of patients with myeloproliferative neoplasms (MPN) including 95% cases of polycythemia vera (PV) and 50-60% cases of essential thrombocythemia (ET) and primary myelofibrosis (PMF). The long-term goals of my laboratory are to elucidate the role of the JAK/STAT pathway in normal hematopoiesis and hematologic diseases. We are using molecular and cell biology, genetic and biochemical approaches to accomplish these goals. We have generated tissue-specific knock-out and knock-in mice models to define the role of the JAK/STAT pathway in the maintenance and function of hematopoietic stem cells and in the pathogenesis of myeloid neoplasms/leukemias. We are also using these mice models to test novel therapies for myeloid neoplasms/leukemias.